TL;DR

If H5N1 flu gains the ability to spread between people, it could readily become a pandemic. Thus, it is very important to know whether it is spreading between people, but no one is currently testing for person-person spread. We are asking for funding to do this testing in the highest risk areas.

Short summary 

We are a group of researchers at Stanford University, led by Dr. Benjamin Pinsky, seeking funding to screen Influenza A-positive samples from hospitals and clinics near infected dairy herds in the California Central Valley for H5N1 influenza. Currently, public health labs are only testing people with known exposure to infected animals for H5N1, so cases of human-to-human transmission would go undiagnosed. We seek to expand surveillance to people from high-risk areas with influenza A infection but without known animal exposure. 

Summary 

There is an ongoing outbreak of H5N1 influenza in dairy cows with >50 associated human infections, the majority of which have occurred near farms in California’s Central Valley. Each infection provides the virus with another opportunity to evolve, and if the virus gains the ability to spread between people, it could rapidly become a pandemic. Current CDC criteria for H5 testing include having known exposure to infected animals. Therefore, if human-human spread occurs, the current testing regime will miss it. To catch potential cases of human-human transmission, we have developed an H5 subtyping assay and are currently testing all influenza A-positive samples within our hospital system for H5, without regard to whether the patient had exposure to animals. We want to expand this surveillance to areas with the most infected cows and humans. We have agreements with hospitals in the Central Valley to send us their untyped Flu A positive samples. We seek funding to start testing as soon as possible and continue through the coming flu season. Testing costs $15USD/sample. We are asking for ~$75,000, but we would readily be able to utilize any amount of funding from thousands to hundreds of thousands of dollars. Without external funding this surveillance will not occur. 

Impact

Of the 889 human cases of H5N1 that are known to have occurred from 2003 to April 1st, 2024, there were 463 deaths (a 52% case fatality rate^[1]). While the current outbreak of clade 2.3.4.4b has mostly caused conjunctivitis with mild flu symptoms, there have been more severe respiratory infections, including a Canadian teenager currently in critical condition and a fatal case of pneumonia. It is therefore possible that disease severity depends on the route of exposure, and as far as we know, there isn't any known barrier to the evolution of respiratory transmissibility. Given that the human population has little to no pre-existing immunity to this virus, if it gains the ability to spread from human to human, it would have the potential to spread rapidly. If the virus gains respiratory transmissibility and remains relatively mild in most patients, it could still conceivably result in a major pandemic. In the worst-case scenario of the virus gaining respiratory transmissibility and reverting to its historical severity, a catastrophic pandemic is possible. 

We believe that the ongoing outbreak in dairy cows represents a real pandemic threat that is not being taken seriously enough. We believe that cases of human-to-human transmission may be occurring and that identifying such cases may spur more decisive action. The prospect of reassortment through co-infection with seasonal influenza strains this winter also creates substantial risk for development of viruses with novel properties. Accelerating the response to the outbreak may decrease the likelihood that it becomes a pandemic. Testing people with confirmed (un-subtyped) Influenza A in regions with the highest concentration of infected animals and people is an efficient way to increase surveillance of the population with highest probability of infection. 

Methods

We have formed a partnership with a network of eight hospitals in California’s Central Valley which are in close proximity to many infected dairy herds and cases of human infection. These hospitals will send us samples which have already been found to be positive for Influenza-A, but have not been tested for H5. They will send us samples that do not meet criteria for testing by public health labs and would otherwise not be tested for H5. Public health labs will continue to test samples that meet their criteria. On the samples sent to us, we will perform multiplex dual-target RT-PCR subtyping for Avian Influenza A(H5). To increase capacity and cost efficiency, tests will be performed on pools of 8 samples, enabling testing of approximately 400 samples per testing run. Positives will be confirmed, sequenced, and tested for other influenza A subtypes to detect potential co-infection. Based on incidence of influenza A during the ‘23/’24 Flu season, we expect to have access to ~5000-6500 samples. 

About the team 

Dr. Benjamin A. Pinsky is a Professor of Pathology and Medicine at the Stanford University School of Medicine and Medical Director of the Clinical Virology Laboratory at Stanford Health Care. He is a leader in the field of infectious disease diagnostics broadly, and viral diagnostics in particular. He has recently published a novel H5 assay and a review on testing strategy for H5N1. The laboratory has a highly skilled staff, many of whom have the experience of rapidly scaling up testing during the COVID-19 pandemic. We have the laboratory infrastructure capable of performing thousands of tests per day. Dr. Grant Higerd-Rusli is a Resident Physician and Post-doctoral Scholar at Stanford University who studies interventions for pandemic prevention. Dr. Abraar Karan is an Infectious Disease Physician Research Fellow at Stanford University and expert in emerging infections.

1. ^{^}

   The true number of cases is likely greater than the number of known cases, so the true case fatality rate is likely lower.